Abstract Postoperative delirium is one of the most common complications following cardiac surgery, with an incidence of up to 50%. Apart from its psychological and physical toll on patients and caregivers, delirium interferes with rehabilitation. It places compromised individuals at risk for self-injury and falls. Given that delirium is associated with subsequent long-term cognitive impairment, elucidation of acute precipitating factors may lend insight into the chronic pathological processes underlying Alzheimer's disease and related dementias. Biomarkers are urgently needed to advance efforts aimed at characterizing postoperative delirium susceptibility, onset, and recovery. Development of these biomarkers would also serve as a major step toward clarifying pathophysiologic mechanisms. Electroencephalographic (EEG) signatures used in defining sleep architecture have potential to address these voids. Their characterization in the postoperative period is also essential for evaluating perioperative sleep disruption as a contributor and predictor of delirium. Our proposal, Postoperative Delirium and Electroencephalographic Measures of Sleep and Wakefulness, is designed to probe temporal relationships between delirium and well-characterized EEG signatures that predict cognitive dysfunction. Future preoperative stratification for delirium vulnerability could inform patients and their families regarding the likelihood of potential cognitive trajectories after elective procedures. For health care practitioners, identification of susceptible patients before surgery could focus diagnostics and optimization. The proposed work may also contribute to novel pharmacologic and non-pharmacologic interventions. Such therapies would target underlying thalamocortical circuits and the expression of specific EEG motifs to impact cognitive recovery. Overall, we expect this work to yield inexpensive, noninvasive, and readily translatable biomarkers, thereby improving neurological outcomes within and beyond perioperative medicine.